scholarly journals The Inhibitory Effect of Cordycepin on the Proliferation of MCF-7 Breast Cancer Cells, and Its Mechanism: An Investigation Using Network Pharmacology-Based Analysis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 414 ◽  
Author(s):  
Dahae Lee ◽  
Won-Yung Lee ◽  
Kiwon Jung ◽  
Yong Kwon ◽  
Daeyoung Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Brown Rice ◽  
Gene Set Enrichment Analysis ◽  
Inhibitory Effects ◽  
Anticancer Effects ◽  
Ic50 Value ◽  
Mcf 7

Cordyceps militaris is a well-known medicinal mushroom. It is non-toxic and has clinical health benefits including cancer inhibition. However, the anticancer effects of C. militaris cultured in brown rice on breast cancer have not yet been reported. In this study, we simultaneously investigated the anticancer effects of cordycepin and an extract of C. militaris cultured in brown rice on MCF-7 human breast cancer cells using a cell viability assay, cell staining with Hoechst 33342, and an image-based cytometric assay. The C. militaris concentrate exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 73.48 µg/mL. Cordycepin also exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 9.58 µM. We applied network pharmacological analysis to predict potential targets and pathways of cordycepin. The gene set enrichment analysis showed that the targets of cordycepin are mainly associated with the hedgehog signaling, apoptosis, p53 signaling, and estrogen signaling pathways. We further verified the predicted targets related to the apoptosis pathway using western blot analysis. The C. militaris concentrate and cordycepin exhibited the ability to induce apoptotic cell death by increasing the cleavage of caspase-7 -8, and -9, increasing the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) protein expression ratio, and decreasing the protein expression of X-linked inhibitor of apoptosis protein (XIAP) in MCF-7 cells. Consequently, the C. militaris concentrate and cordycepin exhibited significant anticancer effects through their ability to induce apoptosis in breast cancer cells.

scholarly journals The Inhibitory Effect of Cordycepin on the Proliferation of MCF-7 Breast Cancer Cells, and its Mechanism: An Investigation Using Network Pharmacology-Based Analysis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 407 ◽  
Author(s):  
Lee ◽  
Lee ◽  
Jung ◽  
Kwon ◽  
Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Brown Rice ◽  
Gene Set Enrichment Analysis ◽  
Inhibitory Effects ◽  
Anticancer Effects ◽  
Ic50 Value ◽  
Mcf 7

Cordyceps militaris is a well-known medicinal mushroom. It is non-toxic and has clinical health benefits including cancer inhibition. However, the anticancer effects of C. militaris cultured in brown rice on breast cancer have not yet been reported. In this study, we simultaneously investigated the anticancer effects of cordycepin and an extract of C. militaris cultured in brown rice on MCF-7 human breast cancer cells using a cell viability assay, cell staining with Hoechst 33342, and an image-based cytometric assay. The C. militaris concentrate exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 73.48 µg/mL. Cordycepin also exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 9.58 µM. We applied network pharmacological analysis to predict potential targets and pathways of cordycepin. The gene set enrichment analysis showed that the targets of cordycepin are mainly associated with the hedgehog signaling, apoptosis, p53 signaling, and estrogen signaling pathways. We further verified the predicted targets related to the apoptosis pathway using western blot analysis. The C. militaris concentrate and cordycepin exhibited the ability to induce apoptotic cell death by increasing the cleavage of caspase-7 -8, and -9, increasing the Bax/Bcl-2 protein expression ratio, and decreasing the protein expression of XIAP in MCF-7 cells. Consequently, the C. militaris concentrate and cordycepin exhibited significant anticancer effects through their ability to induce apoptosis in breast cancer cells.

scholarly journals The Synthesis of Cinchonine Tiglat Ester Compound and Cytotoxic Test Against MCF-7 Breast Cancer Cell

2018 ◽  
Vol 19 (2) ◽  
pp. 54-61
Author(s):  
Ahmad Khanifudin ◽  
Gian Primahana ◽  
Sylvia Rizky Prima ◽  
Puspa Dewi Lotulung ◽  
Muhammad Hanafi
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cinchona Alkaloid ◽  
Alamar Blue ◽  
Tiglic Acid ◽  
Spectroscopy Instrumentation ◽  
Ic50 Value ◽  
Pass Through ◽  
Mcf 7

Cinchonine is a type of cinchona alkaloid compound commonly found and/or isolated from Cinchona sp. plant. It is commonly used to treat malaria, and can potentially be used against cancer cells. In this particular study, cinchonine ester derivatives were extracted through esterification processs. Synthesized esther is aimed to gain higher lipophilicity of cinchonine so that makes it easier to pass through cell membrane. Esterification was done using DCC activator as well as DMAP catalyst with tiglic acid used to create cinchonine tiglat. Subsequent cinchonine tiglat was obtained in the form of oil with 25,28% yield. The compound obtained from the synthesis was the analyzed using LC-ESI-MS and 1H-NMR spectroscopy instrumentation. Results show that the target compound has been successfully synthesized. Its cytotoxic ability against MCF-7 breast cancer cells was tested using the Alamar Blue method. Results concluded that cinchonine tiglat ester compound has a viable cytotoxic activity with IC50 value of 1.22 ppm.

scholarly journals Micronutrients Selenomethionine and Selenocysteine Modulate the Redox Status of MCF-7 Breast Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 865 ◽  
Author(s):  
Daniel Gabriel Pons ◽  
Carmen Moran ◽  
Marina Alorda-Clara ◽  
Jordi Oliver ◽  
Pilar Roca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hydrogen Peroxide ◽  
Antioxidant Enzymes ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Redox Status ◽  
Hydrogen Peroxide Production ◽  
Low Concentrations ◽  
Mcf 7

Selenium is a micronutrient which is found in many foods, with redox status modulation activity. Our aim was to evaluate the effects of two chemical forms of selenoamino acids, Seleno-L-methionine and Seleno-L-cystine (a diselenide derived from selenocysteine), at different concentrations on cell viability, hydrogen peroxide production, antioxidant enzymes, UCP2 protein expression, as well as lipid and protein oxidative damage in MCF-7 breast cancer cells. Results showed that Seleno-L-methionine did not cause an increase in hydrogen peroxide production at relatively low concentrations, accompanied by a rise in the antioxidant enzymes catalase and MnSOD, and UCP2 protein expression levels. Furthermore, a decrease in protein and lipid oxidative damage was observed at 10 µM concentration. Otherwise, Seleno-L-cystine increased hydrogen peroxide production from relatively low concentrations (100 nM) to a large increase at high concentrations. Moreover, at 10 µM, Seleno-L-cystine decreased UCP2 and MnSOD protein expression. In conclusion, the chemical form of selenoamino acid and their incorporation to selenoproteins could affect the regulation of the breast cancer cell redox status. Taken together, the results obtained in this study imply that it is important to control the type of selenium-enriched nutrient consumption, taking into consideration their composition and concentration.

scholarly journals Inhibition of STAT3 enhances sensitivity to tamoxifen in tamoxifen-resistant breast cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seo Yun Moon ◽  
Heejin Lee ◽  
Seoree Kim ◽  
Ji Hyung Hong ◽  
Sang Hoon Chun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Signalling Pathway ◽  
Expression Levels ◽  
Er Positive ◽  
Tamoxifen Resistant ◽  
Stat3 Signalling ◽  
Mcf 7

Abstract Background The mechanisms of endocrine resistance are complex, and deregulation of several oncogenic signalling pathways has been proposed. We aimed to investigate the role of the EGFR and Src-mediated STAT3 signalling pathway in tamoxifen-resistant breast cancer cells. Methods The ER-positive luminal breast cancer cell lines, MCF-7 and T47D, were used. We have established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen. Cell viability was determined using an MTT assay, and protein expression levels were determined using western blot. Cell cycle and annexin V staining were analysed using flow cytometry. Results TamR cells showed decreased expression of estrogen receptor and increased expression of EGFR. TamR cells showed an acceleration of the G1 to S phase transition. The protein expression levels of phosphorylated Src, EGFR (Y845), and STAT3 was increased in TamR cells, while phosphorylated Akt was decreased. The expression of p-STAT3 was enhanced according to exposure time of tamoxifen in T47D cells, suggesting that activation of STAT3 can cause tamoxifen resistance in ER-positive breast cancer cells. Both dasatinib (Src inhibitor) and stattic (STAT3 inhibitor) inhibited cell proliferation and induced apoptosis in TamR cells. However, stattic showed a much stronger effect than dasatinib. Knockdown of STAT3 expression by siRNA had no effect on sensitivity to tamoxifen in MCF-7 cells, while that enhanced sensitivity to tamoxifen in TamR cells. There was not a significant synergistic effect of dasatinib and stattic on cell survival. TamR cells have low nuclear p21(Cip1) expression compared to MCF-7 cells and inhibition of STAT3 increased the expression of nuclear p21(Cip1) in TamR cells. Conclusions The EGFR and Src-mediated STAT3 signalling pathway is activated in TamR cells, and inhibition of STAT3 may be a potential target in tamoxifen-resistant breast cancer. An increase in nuclear p21(Cip1) may be a key step in STAT3 inhibitor-induced cell death in TamR cells.

scholarly journals Annexin A1 is responsible for ursolic acid mediated anticancer effects on breast cancer stem cells by wnt/β-catenin pathway

2020 ◽  
Author(s):  
shujun fan ◽  
Ruixue Xu ◽  
Han Zhang ◽  
Jun Mao ◽  
Qingqing Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Stem Cells ◽  
Annexin A1 ◽  
Qrt Pcr ◽  
Anticancer Effects ◽  
Mcf 7

Abstract Background Ursolic acid (UA), a plant extract from traditional Chinese medicines as well as edible vegetables, exhibits a potent anticancer activity in various tumor cells. Annexin A1(AnxA1) is dysregulated and play a pivotal role in various tumor. However, the function of AnxA1 in breast cancer(BC) remains unclear. Methods Western blot, real-time quantitative polymerase chain reaction(qRT- PCR), transwell, wound healing and immunofluorescence were used to study the biological features of AnxA1 in breast cancer. The stemness of cancer cells was assessed by sphere formation assay. CCK-8 and flow cytometry assay were used to detect the effects of ursolic acid on the growth, proliferation and apoptosis of breast cancer cells in vitro. A nude mice xenograft model was employed in vivo. The potential mechanism by which Ursolic acid regulates the biological behaviors of breast cancer stem cells through AnxA1 via the wnt/β-catenin signaling pathway was tested by western blot, qRT- PCR and immunohistochemistry. Results AnxA1 was highly expressed in MDA-MB-231 cell line compared with MCF-7 cell line, Down-regulation of AnxA1 could reduce the mammosphere formation, inhibit EMT, decrease the ability of migration and invasion in MCF-7 and MDA-MB-231 cells. Ursolic acid can reduce the expression of AnxA1 and inhibit proliferation of breast cancer cells, stemness, EMT, migration and invasion, promote cell apoptosis of breast cancer cell. This studies suggest that the anticancer effects of AnxA1 knockdown and UA treatment may be realized by affecting the EMT process and the wnt/β-catenin signaling pathway. Conclusions This research suggest that AnxA1 knockdown enhanced the sensitivity of breast cancer cells to UA, the combination of UA treatment and AnxA1 knockdown possesses multiple anti-tumor activities against breast cancer, as it, in particular, inhibited the cancer stem cell and attenuated EMT. Therefore, it is emerging as a promising therapeutic strategy to inhibit breast cancer.

scholarly journals CYTOTOXIC ACTIVITY AND SELECTIVITY INDEX OF BINAHONG (Anredera cordifolia) EXTRACTS ON MCF-7 BREAST CANCER CELLS AND VERO NORMAL CELLS LINE

2021 ◽  
Vol 3 (2) ◽  
pp. 72-80
Author(s):  
Dita Sozianty ◽  
Rifki Febriansah
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Selectivity Index ◽  
Cytotoxic Agents ◽  
Flavonoid Compounds ◽  
Ic50 Value ◽  
Her 2 ◽  
Mcf 7

Background: Breast cancers occur because of an impaired balance between proliferation, differentiation, and apoptosis of breast glands. Natural products have potency as cytotoxic agents with less side effects than chemotherapy. One of the potential plants is Anredera cordifolia (Ten.) Stennis (binahong), which contains flavonoid 8-glucopyranosyl- 4’,5,7-trihydroxy flavone compounds.Objective: This study aims to determine the potency of binahong leaves extract as an anticancer for breast cancer in vitro and in silico.Methods: Preliminary tests using molecular docking of 8-glucopyranosyl-4’,5,7-trihydroxyflavone compounds on Bcl-2 and HER-2 proteins. The extraction and fractionation were to obtain binahong extract. Thin layer chromatography to identify flavonoid compounds in the extract. DPPH assay was performed to evaluate the antioxidant activity. MTT assay was performed to evaluate cytotoxic activity on MCF-7 breast cancer cells and Vero cells.Results: In silico test showed a stable bond between 8-glucopyranosyl- 4’,5,7-trihydroxylflavone, and Bcl-2 and HER-2 with a docking score of -7.5 kcal/mol and -8.0 kcal/mol, respectively. The binahong extract contain flavonoid compounds that had the retention factor value 0.78; 0.49; 0.35. Antioxidant test resulted IC50 value of 4940 μg/mL. Cytotoxic test resulted in IC50 value of 1073 μg/mL and 486 μg/mL for Vero cells and MCF-7 breast cancer cells, respectively. The comparison between IC50 produced a selectivity index value of 2.149, which shows that binahong extract was selective against MCF-7 breast cancers.Conclusion: This study concluded that binahong extract has weak potency as anticancer agent on MCF-7 cells.

Anti-carcinogenic effect of Cathepsin K Inhibitor, Odanacatib with low dose of Cisplatin Against Human Breast Carcinoma MCF-7 and MDAMB231 Cells

2020 ◽  
Vol 16 ◽  
Author(s):  
Yaongamphi Vashum ◽  
Amuthavalli Kottaiswamy ◽  
Tholcopiyan Loganathan ◽  
Fathima Bushra Sheriff ◽  
Shila Samuel
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Low Dose ◽  
Cathepsin K ◽  
Platinum Compound ◽  
Alternative Treatment Option ◽  
Mcf 7

Background: A cross-linking agent commonly used for cancer chemotherapy is a platinum compound such as cisplatin. However, with the acquisition of cellular drug resistance and adverse side effects, the potency of cisplatin is therefore, often tempered. To overcome these, the present study has established the use of cathepsin k (CTSK) inhibitor as a potent chemo sensitizer. Methods: The cytotoxic effect of cisplatin and odanacatib (ODN) on two different breast cancer patient-derived cell lines, MDA-MB-231 and MCF-7, was assessed by MTT-based colorimetric assay. The drug interaction coefficient CDI was used to evaluate the synergistically inhibitory impact of the drug combination and immunoblot was used to examine protein expression of certain proteins responsible for cell survival and the mechanism of apoptosis. Results: In this study, we found that IC50 of ODN in combination with cisplatin (half of IC25) induces a synergistic cytotoxic effect in different breast cancer cells. Diminished expression of Bcl-2 and increased expression of Bax aroused the cytochrome release, that triggers caspase-9 and -3 activation in the combinatorial group. ODN with lower dose of cisplatin significantly inhibits the protein expression of novel chemoresistant factors such as STAT3, NFҡB and IL-6. Conclusion: This study highlights the potential effects of the combination of ODN with reduced dose of cisplatin on improving the growth inhibition and apoptosis-inducing effect on breast cancer cells via combined inhibition of NF-κBinduced IL-6 and STAT3 activation.The study result suggests that the further development of this novel inhibitor combination with low dose of standard cisplatin-based chemotherapy may contribute to alternative treatment option for certain cancers.

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